These experiments have two broad objectives. First, we intend to localize and better characterize the brain sodium-receptor mechanisms involved in the central induction of changes in renal sodium excretion (UNaV) and renin secretion. Achievement of this objective will enable us to better evaluate whether these receptors have any day-to-day phySiological significance. Secondly, we will study the efferent and renal mechanisms by which the changes in renin and UNaV are brought about. Regardless of the physiologic significance of the central receptors, we can capitalize on the fact that the CNS stimuli are known to be potent in affecting UNaV and renin in the absence of major physical changes within the circulatory system. We can thus use the CNS stimuli as a tool to achieve our second objective, i.e., to study the mechanisms controlling UNaV and renin. Experiments will be carried out in dogs and rats, both anesthetized and unanesthetized animals. The CNS mechanism of response to changes in brain sodium will be evaluated using ventriculo-cisternal perfusion (controlled levels of non-sodium electrolytes) and localized "push-pull" perfusions. Sodium concentrations will be changed moderately while osmolarity is controlled. We will also perfuse drugs with documented effects on brain intracellular sodium to test the hypothesis that the CSF electrolyte changes act by changing intracellular sodium concentration. We will localize the site of stimulus action via localized push-pull perfusions, and ablation of hypothetical receptor locations. The mechanism of the renal response to an antinatriuretic CNS stimulus is independent of changes in blood pressure, GFR, and RPF; we will evaluate the extent to which this holds for the natriuretic CNS stimulus by contriving either no change or reduced renal arterial pressure and GFR during the CNS stimulus. "Natriuretic activity" will be assayed in these experiments through a collaborative arrangement. BIBLIOGRAPHIC REFERENCES: Clamage, D. M., Sanford, C. S., Vander, A. J. and Mouw, D. R.: Effects of psychosocial stimuli on plasma renin activity in rats. Amer. J. Physiology 231:1290-1294, 1976.